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Neuroendocrine response to clonidine and 8‐OH‐DPAT in rats following chronic administration of desipramine or sertraline
Author(s) -
O'Donnell J.M.,
Grealy M.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09069.x
Subject(s) - desipramine , sertraline , endocrinology , medicine , clonidine , prolactin , 8 oh dpat , dihydroalprenolol , corticosterone , serotonin , chemistry , hormone , agonist , 5 ht receptor , receptor , antidepressant , partial agonist , hippocampus
1 Rats were administered either desipramine (DMI) or sertraline daily at doses 7.5 mg kg −1 or 10 mg kg −1 , i.p., respectively and the effects on the functional state of hypothalamic neuroendocrine control mechanisms assessed by measurements of plasma hormones following acute drug challenge. The effects of treatment on gross behaviour and brain adrenoceptor density were also determined. 2 Both DMI and sertraline caused significant reduction in activity measured as ambulation and rearing at 14 days of treatment. 3 All animals were chronically cannulated after 14 days of treatment and tested for neuroendocrine response to acute i.v. clonidine (50 μg kg −1 ) or 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT, 250 μg kg −1 ) after 21 or more days of treatment. 4 Rats treated with DMI but not sertraline showed a virtually complete suppression of the growth hormone (GH) secretion elicited by clonidine in controls, while the secretion of corticosterone was augmented. 5 Treatment with DMI but not sertraline led to a significantly greater 8‐OH‐DPAT‐induced secretion of prolactin than in the control rats, while the plasma concentrations of corticosterone following 8‐OH‐DPAT were not influenced by either DMI or sertraline treatment. 6 The density (but not the affinity) of cerebral cortical binding of [ 3 H]‐dihydroalprenolol was significantly reduced by DMI treatment. 7 These results show that DMI treatment blunted the sensitivity of post‐synaptic α 2 ‐adrenoceptors, accompanied by complex interactions manifested as increased responsiveness of α 1 ‐adrenoceptors and 5‐HT 1A receptors. Sertraline had no significant neurendocrine effects at a dose which significantly reduced gross activity.